The inactivation of the retinoblastoma tumor suppressor protein Rb by cell cycle regulatory kinases is disrupted in almost all cancers. In normal cells, inactivation of Rb is necessary for the G1 to S phase progression of the cell cycle. Rb controls entry into the S phase by repressing the transcriptional activity of the E2F family of transcription factors, especially E2Fs 1, 2, and 3. Rb is inactivated through multiple phosphorylation events mediated by kinases associated with D and E type cyclins in the G1 phase of the cell cycle. It was found that the signaling kinase Raf-1 initiates the phosphorylation events; Raf-1 signaling kinase is known to play a role in promoting cancer, and studies have shown that Rb:Raf-1 binding facilitates cell proliferation. It has also been found that the Rb:Raf-1 interaction is elevated in human tumors compared to adjacent normal tissue in 80% of samples examined. Because Raf-1 is persistently activated in many tumors, a few attempts have been made to selectively inhibit tumors by modulating Rb and/or Raf-1 activity with Raf-1 antisense oligonucleotides, the multikinase inhibitor Sorafenib, and a peptide fragment of Raf-1 coupled to a carrier peptide. However, there is still a need for effective modulators of the Rb:Raf-1 interaction.